LSD: Difference between revisions

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{{MedTemplate

| generic = LSD

| brand =

| brand = Delysid (historical, Sandoz, withdrawn 1965)

| structure =

| classes = Classic Psychedelic, Lysergamide

| classes = Classic Psychedelic, Ergoline, Lysergamide

| ~~mechanism~~ = ~~5-HT2A agonist; D2 partial agonist~~

| uses =

| ~~uses~~ =

| starting_dose =

| ~~starting_dose~~ =

| preparations =

| ~~preparations~~ =

| fda_max =

| ~~fda_max~~ =

| pill_id =

| routes =

| routes = Oral

| onset =

| onset = 30–60 minutes

| duration =

| duration = 8–12 hours

| halflife =

| halflife = 3–5 hours

| bioavailability =

| bioavailability = 70–90% (oral)

| pregnancy =

| pregnancy = Not established

| legal =

| legal = Schedule I (United States)

| ~~intro~~ =

| mechanism = 5-HT2A partial agonist

| ~~pharmacokinetics~~ =

| intro = LSD, lysergic acid diethylamide, is the archetypal pharma psychedelic, a semisynthetic ergoline first prepared in 1938 by the Swiss chemist Albert Hofmann at Sandoz Laboratories in Basel. The molecule's psychoactivity was discovered five years later, on 16 April 1943, when Hofmann was accidentally exposed to the compound while recrystallizing the tartrate salt and three days later took a deliberate 250 microgram dose; the bicycle ride home from his laboratory on 19 April 1943 has been remembered in the pharmacological tradition as Bicycle Day. Sandoz marketed LSD to researchers in the 1950s and 1960s under the trade name Delysid for use in psychiatric research, and the compound shaped a generation of work on serotonin, the model-psychosis hypothesis, and the foundations of modern psychopharmacology before its abrupt removal from clinical research in the late 1960s.

| ~~pharmacodynamics~~ =

| history = The story of LSD begins not with the molecule but with ergot, the fungus Claviceps purpurea, which infects rye and other grains and was responsible for the medieval European epidemics known as St. Anthony's Fire, marked by gangrene, convulsions, and hallucinations. Ergot was a known toxin and a known abortifacient and obstetric agent in folk medicine; its alkaloid pharmacology became a subject of systematic chemistry only in the early 20th century. At Sandoz in Basel, the chemist Arthur Stoll isolated ergotamine in 1918, and through the 1930s the Sandoz pharmaceutical laboratory pursued ergot alkaloid chemistry as a commercial research program. Albert Hofmann joined the laboratory in 1929 and was set to work systematically modifying the lysergic acid skeleton in search of medically useful derivatives.

~~| indications =~~

~~| dosing =~~

The 25th compound in Hofmann's series, the diethylamide of lysergic acid, was first synthesized on 16 November 1938 and given the laboratory designation LSD-25. Pharmacological screening at the time showed only modest uterine-contractile activity, and the compound was set aside. Hofmann re-synthesized LSD-25 in April 1943 on what he later described as a hunch. On 16 April 1943, during the recrystallization of the tartrate salt, Hofmann became unwell, left the laboratory, and experienced what he would later describe as a dreamlike state of vivid imagination. The route of exposure on 16 April was almost certainly accidental ingestion via hand-to-mouth contamination during the laboratory work; the transdermal-absorption account that has attached to the story is folklore, since LSD does not cross intact skin in pharmacologically active quantities at the scale of exposure that recrystallization would produce.

| effects =

| ~~contraindications~~ =

Three days later, on 19 April 1943, Hofmann took a measured dose of 250 micrograms of LSD, an amount he calculated as one tenth of a minimal active dose based on his knowledge of other ergot alkaloids. The dose was in fact an enormous overdose; the threshold dose of LSD is around 20 micrograms. The effects came on rapidly. Hofmann left the Sandoz laboratory and bicycled the four kilometers home accompanied by his laboratory assistant, the wartime fuel restrictions in Switzerland having made other transport unavailable. During the ride and at home he experienced acute fear that he was dying or losing his mind; he asked his assistant to call a doctor, who examined him and found his vital signs normal. The experience resolved over the following hours into what Hofmann described as a state of great peace and aesthetic intensity. The 19 April 1943 session is the first deliberate human dose of LSD, the founding event of the medicine's history, and the source of the Bicycle Day designation.<ref>Stoll WA. Lysergsäure-diäthylamid, ein Phantastikum aus der Mutterkorngruppe. Schweizer Archiv für Neurologie und Psychiatrie. 1947;60:279-323.</ref><ref>Hofmann A. LSD: My Problem Child. New York: McGraw-Hill; 1980.</ref>

| ~~interactions~~ =

| ~~pregnancy_details~~ =

Sandoz registered the trade name Delysid and from 1949 distributed LSD free of charge to researchers and clinicians worldwide, with the suggestion that the medicine might be useful in psychotherapy and in giving clinicians experimental access to states resembling psychotic illness. Through the 1950s and into the 1960s, several hundred clinical and research papers were published on LSD. Humphry Osmond, the British-Canadian psychiatrist working in Saskatchewan, proposed the word "psychedelic" in 1957 in correspondence with Aldous Huxley to describe the class of effects the medicine produced. The United States Central Intelligence Agency's Project MKUltra, beginning in 1953, conducted covert research on LSD as a potential agent of interrogation and behavior modification; the program ran for two decades before being exposed by congressional investigation in the 1970s.

| ~~monitoring~~ =

~~| counseling~~ =

{{PendellsCorner

| ~~anecdotes~~ =

| quote = Hofmann succeeded easily where the CIA had failed, isolated the magic of the mushrooms and in an act of shamanic propriety, made the long journey to Huautla, to present his molecules to Maria Sabina.

| seealso =

| volume = Gnosis

| references =

| page = 53

}}

The cultural rupture of the 1960s ended the Sandoz era. LSD escaped the clinical research apparatus through Timothy Leary and Richard Alpert's work at Harvard, through Ken Kesey's Merry Pranksters and the broader American counterculture, and through the rapid scaling of unregulated production. In 1965 Sandoz ceased distribution and withdrew the Delysid trade name. The United States Drug Abuse Control Amendments of 1965 brought LSD under federal control; the Controlled Substances Act of 1970 placed it in Schedule I, the most restrictive category. Human research effectively halted for the next three decades.

The reopening came in Switzerland. The Swiss psychiatrist Peter Gasser obtained regulatory permission in 2007 to administer LSD-assisted psychotherapy to patients with anxiety associated with life-threatening illness, the first formal LSD clinical trial in nearly forty years.<ref>Gasser P, Holstein D, Michel Y, Doblin R, et al. Safety and efficacy of lysergic acid diethylamide-assisted psychotherapy for anxiety associated with life-threatening diseases. The Journal of Nervous and Mental Disease. 2014;202(7):513-520. PMID: 24594678.</ref> Modern dose-response and pharmacology work on LSD has been led primarily by Matthias Liechti's group at the University Hospital Basel.<ref>Schmid Y, Enzler F, Gasser P, Grouzmann E, et al. Acute effects of lysergic acid diethylamide in healthy subjects. Biological Psychiatry. 2015;78(8):544-553. PMID: 25575620.</ref><ref>Holze F, Vizeli P, Ley L, Müller F, et al. Acute dose-dependent effects of lysergic acid diethylamide in a double-blind placebo-controlled study in healthy subjects. Neuropsychopharmacology. 2021;46(3):537-544. PMID: 33059356.</ref> The compound has been examined in cluster headache,<ref>Sewell RA, Halpern JH, Pope HG Jr. Response of cluster headache to psilocybin and LSD. Neurology. 2006;66(12):1920-1922. PMID: 16801660.</ref> in anxiety associated with life-threatening illness in a randomized placebo-controlled phase II trial,<ref>Holze F, Gasser P, Müller F, Dolder PC, et al. Lysergic acid diethylamide-assisted therapy in patients with anxiety with and without a life-threatening illness: a randomized, double-blind, placebo-controlled phase II study. Biological Psychiatry. 2023;93(3):215-223. PMID: 36266118.</ref> and in long-term follow-up of the same patient population.<ref>Holze F, Gasser P, Müller F, Strebel M, et al. LSD-assisted therapy in patients with anxiety: open-label prospective 12-month follow-up. The British Journal of Psychiatry. 2024;225(3):362-370. PMID: 39078038.</ref> LSD remains a Schedule I controlled substance in the United States and is restricted under the 1971 United Nations Convention on Psychotropic Substances; current clinical research operates under regulatory exemption frameworks, with no approved medical indication.

| pharmacodynamics = LSD is a semisynthetic ergoline, the diethylamide of d-lysergic acid, prepared from lysergic acid obtained by alkaline hydrolysis of natural ergot alkaloids. The molecule binds at multiple monoamine receptors with extraordinary affinity, but its psychedelic effects are driven primarily by partial agonism at the serotonin 5-HT2A receptor; ketanserin-blockade studies in humans confirm that 5-HT2A action is necessary for the subjective experience.<ref>Nichols DE. Psychedelics. Pharmacological Reviews. 2016;68(2):264-355. PMID: 26841800.</ref> LSD also binds at 5-HT1A, 5-HT2C, 5-HT6, 5-HT7, dopamine D1 through D5, and adrenergic receptors with affinities in the nanomolar range; the contribution of these non-5-HT2A actions to the overall psychopharmacology remains incompletely characterized.<ref>Passie T, Halpern JH, Stichtenoth DO, Emrich HM, et al. The pharmacology of lysergic acid diethylamide: a review. CNS Neuroscience & Therapeutics. 2008;14(4):295-314. PMID: 19040555.</ref>

The compound is unusually potent: threshold psychedelic effects in humans are produced by doses of approximately 20 micrograms, and full psychedelic doses are 100 to 200 micrograms orally. Onset is typically 30 to 60 minutes; the experience reaches plateau at two to three hours and is essentially complete by eight to twelve hours, with residual effects in some subjects extending beyond. The unusually long duration relative to other 5-HT2A agonists is thought to reflect slow dissociation kinetics at the receptor.

Doses used outside the controlled-trial setting are not standardized. Harm-reduction documentation such as the Erowid LSD Vault records non-clinical oral use extending well above the 100 to 200 micrograms typical of supervised research, into the range of several hundred micrograms.<ref name="erowid-lsd-dose">Erowid. LSD Dosage. Erowid LSD Vault, 1997, last modified 20 February 2017. https://www.erowid.org/chemicals/lsd/lsd_dose.shtml (accessed 20 May 2026).</ref> Because LSD is active at microgram quantities, the amount contained in any non-pharmaceutical unit is inherently uncertain, a point of practical relevance when a clinician is assessing a patient's reported exposure.

| interactions = <pharmaInteractions/>

| seealso = [[DMT]], [[Psilocybin]]

| references = <references/>

}}

[[Category:~~Classic_Psychedelics~~]]

[[Category:Pharmaceutical]]

[[Category:Psychedelics]]

[[Category:Classical Psychedelics (Serotonergic)]]

[[Category:Lysergamides]]

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